Synopses

Microsporidiosis is a fungal infection that generally causes digestive disorders, especially in immunocompromised hosts. Over a 4-day period in January 2018, 3 patients with hematologic malignancies who were admitted to the hematology unit of a hospital in France received diagnoses of Enterocytozoon bieneusi microsporidiosis. This unusually high incidence was investigated by sequence analysis at the internal transcribed spacer rDNA locus and then by 3 microsatellites and 1 minisatellite for multilocus genotyping. The 3 isolates had many sequence similarities and belonged to a new genotype closely related to genotype C. In addition, multilocus genotyping showed high genetic distances with all the other strains collected from epidemiologically unrelated persons; none of these strains belonged to the new genotype. These data confirm the epidemiologic link among the 3 patients and support a common source of infection.

We aimed to provide updated epidemiologic data on carbapenem-resistant Klebsiella pneumoniae in Portugal by characterizing all isolates (N = 46) recovered during 2013–2018 in a 123-bed hospital in Lisbon. We identified blaKPC-3 (n = 36), blaOXA-181 (n = 9), and blaGES-5 (n = 8) carbapenemase genes and observed co-occurrence of blaKPC-3 and blaGES-5 in 7 isolates. A single GES-5–producing isolate co-produced the extended-spectrum β-lactamase BEL-1; both corresponding genes were co-located on the same ColE1-like plasmid. The blaOXA-181 gene was always located on an IncX3 plasmid, whereas blaKPC-3 was carried on IncN, IncFII, IncFIB, and IncFIIA plasmid types. The 46 isolates were distributed into 13 pulsotypes and 9 sequence types. All isolates remained susceptible to ceftazidime/avibactam, but some exhibited reduced antimicrobial susceptibility (MIC = 3 mg/L).

To evaluate a classification system to support clinical decisions for treatment of contaminated deep wounds at risk for an invasive fungal infection (IFI), we studied 246 US service members (413 wounds) injured in Afghanistan (2009–2014) who had laboratory evidence of fungal infection. A total of 143 wounds with persistent necrosis and laboratory evidence were classified as IFI; 120 wounds not meeting IFI criteria were classified as high suspicion (patients had localized infection signs/symptoms and had received antifungal medication for >10 days), and 150 were classified as low suspicion (failed to meet these criteria). IFI patients received more blood than other patients and had more severe injuries than patients in the low-suspicion group. Fungi of the order Mucorales were more frequently isolated from IFI (39%) and high-suspicion (21%) wounds than from low-suspicion (9%) wounds. Wounds that did not require immediate antifungal therapy lacked necrosis and localized signs/symptoms of infection and contained fungi from orders other than Mucorales.

Mycobacterium haemophilum is a nontuberculous mycobacterium that can infect immunocompromised patients. Because of special conditions required for its culture, this bacterium is rarely reported and there are scarce data for long-term outcomes. We conducted a retrospective study at Siriraj Hospital, Bangkok, Thailand, during January 2012–September 2017. We studied 21 patients for which HIV infection was the most common concurrent condition. The most common organ involvement was skin and soft tissue (60%). Combination therapy with macrolides and fluoroquinolones resulted in a 60% cure rate for cutaneous infection; adding rifampin as a third drug for more severe cases resulted in modest (66%) cure rate. Efficacy of medical therapy in cutaneous, musculoskeletal, and ocular diseases was 80%, 50%, and 50%, respectively. All patients with central nervous system involvement showed treatment failures. Infections with M. haemophilum in HIV-infected patients were more likely to have central nervous system involvement and tended to have disseminated infections and less favorable outcomes.

Research

Theileria orientalis Ikeda genotype is a parasite that causes a disease in cattle that results in major economic issues in Asia, New Zealand, and Australia. The parasite is transmitted by Haemaphysalis longicornis ticks, which have recently been reported in numerous states throughout the eastern United States. Concurrently, cattle in Virginia showed clinical signs consistent with a hemoprotozoan infection. We used amplicons specific for the major piroplasm surface protein and small subunit rDNA of piroplasms to test blood samples from the cattle by PCR. Bidirectional Sanger sequencing showed sequences with 100% identity with T. orientalis Ikeda genotype 2 sequences. We detected the parasite in 3 unrelated herds and from various animals sampled at 2 time points. Although other benign T. orientalis genotypes are endemic to the United States, detection of T. orientalis Ikeda genotype might represent a risk for the cattle industry in Virginia.

In July 2018, a case of Neisseria gonorrhoeae associated with ceftriaxone treatment failure was identified in Alberta, Canada. We identified the isolate and nucleic acid amplification testing (NAAT) specimen as the ceftriaxone-resistant strain multilocus sequence type 1903/NG-MAST 3435/NG-STAR 233, originally identified in Japan (FC428), with the same penA 60.001 mosaic allele and genetic resistance determinants. Core single-nucleotide variant (SNV) analysis identified 13 SNVs between this isolate and FC428. Culture-independent surveillance by PCR for the A311V mutation in the penA allele and N. gonorrhoeae multiantigen sequence typing directly from NAAT transport media positive for N. gonorrhoeae by NAAT did not detect spread of the strain. We identified multiple sequence types not previously detected in Alberta by routine surveillance. This case demonstrates the benefit of using culture-independent methods to enhance detection, public health investigations, and surveillance to address this global threat.

Candida tropicalis is the leading cause of non–C.albicans candidemia in tropical Asia and Latin America. We evaluated isolates from 344 patients with an initial episode of C. tropicalis candidemia. We found that 58 (16.9%) patients were infected by fluconazole-nonsusceptible (FNS) C. tropicalis with cross resistance to itraconazole, voriconazole, and posaconazole; 55.2% (32/58) of patients were azole-naive. Multilocus sequence typing analysis revealed FNS isolates were genetically closely related, but we did not see time- or place-clustering. Among the diploid sequence types (DSTs), we noted DST225, which has been reported from fruit in Taiwan and hospitals in Beijing, China, as well as DST376 and DST505–7, which also were reported from hospitals in Shanghai, China. Our findings suggest cross-boundary expansion of FNS C. tropicalis and highlight the importance of active surveillance of clinical isolates to detect dissemination of this pathogen and explore potential sources in the community.

Acute flaccid myelitis (AFM) is a polio-like disease that results in paralysis in previously healthy persons. Although the definitive cause of AFM remains unconfirmed, enterovirus D68 (EV-D68) is suspected based on 2014 data demonstrating an increase in AFM cases concomitant with an EV-D68 outbreak. We examined the prevalence in children and the molecular evolution of EV-D68 for 2009–2018 in Philadelphia, Pennsylvania, USA. We detected widespread EV-D68 circulation in 2009, rare detections in 2010 and 2011, and then biennial circulation, only in even years, during 2012–2018. Prevalence of EV-D68 significantly correlated with AFM cases during this period. Finally, whole-genome sequencing revealed early detection of the B1 clade in 2009 and continued evolution of the B3 clade from 2016 to 2018. These data reinforce the need to improve surveillance programs for nonpolio enterovirus to identify possible AFM triggers and predict disease prevalence to better prepare for future outbreaks.

To assess whether risk for Clostridioides difficile infection (CDI) is higher among older adults with cancer, we conducted a retrospective cohort study with a nested case–control analysis using population-based Surveillance, Epidemiology, and End Results–Medicare linked data for 2011. Among 93,566 Medicare beneficiaries, incident CDI and odds for acquiring CDI were higher among patients with than without cancer. Specifically, risk was significantly higher for those who had liquid tumors and higher for those who had recently diagnosed solid tumors and distant metastasis. These findings were independent of prior healthcare-associated exposure. This population-based assessment can be used to identify targets for prevention of CDI.

We used phylogenomic and risk factor data on isolates of Salmonella enterica serovars Mississippi and Typhimurium definitive type 160 (DT160) collected from human, animal, and environmental sources to elucidate their epidemiology and disease reservoirs in Australia and New Zealand. Sequence data suggested wild birds as a likely reservoir for DT160; animal and environmental sources varied more for Salmonella Mississippi than for Salmonella Typhimurium. Australia and New Zealand isolates sat in distinct clades for both serovars; the median single-nucleotide polymorphism distance for DT160 was 29 (range 8–66) and for Salmonella Mississippi, 619 (range 565–737). Phylogenomic data identified plausible sources of human infection from wildlife and environmental reservoirs and provided evidence supporting New Zealand–acquired DT160 in a group of travelers returning to Australia. Wider use of real-time whole-genome sequencing in new locations and for other serovars may identify sources and routes of transmission, thereby aiding prevention and control.

Candida auris is an invasive healthcare-associated fungal pathogen. Cases of candidemia, defined as illness in patients with Candida cultured from blood, were detected through national laboratory-based surveillance in South Africa during 2016–2017. We identified viable isolates by using mass spectrometry and sequencing. Among 6,669 cases (5,876 with species identification) from 269 hospitals, 794 (14%) were caused by C. auris. The incidence risk for all candidemia at 133 hospitals was 83.8 (95% CI 81.2–86.4) cases/100,000 admissions. Prior systemic antifungal drug therapy was associated with a 40% increased adjusted odds of C. auris fungemia compared with bloodstream infection caused by other Candida species (adjusted odds ratio 1.4 [95% CI 0.8–2.3]). The crude in-hospital case-fatality ratio did not differ between Candida species and was 45% for C. auris candidemia, compared with 43% for non–C. auris candidemia. C. auris has caused a major epidemiologic shift in candidemia in South Africa.

We describe the effects of the 7-valent (PCV7) and 13-valent (PCV13) pneumococcal conjugate vaccines on pneumococcal meningitis in England and Wales during July 1, 2000–June 30, 2016. Overall, 84,473 laboratory-confirmed invasive pneumococcal disease cases, including 4,160 (4.9%) cases with meningitis, occurred. PCV7 implementation in 2006 did not lower overall pneumococcal meningitis incidence because of replacement with non–PCV7-type meningitis incidence. Replacement with PCV13 in 2010, however, led to a 48% reduction in pneumococcal meningitis incidence by 2015–16. The overall case-fatality rate was 17.5%: 10.7% among patients <5 years of age, 17.3% among patients 5–64 years of age, and 31.9% among patients >65 years of age. Serotype 8 was associated with increased odds of death (adjusted odds ratio 2.9, 95% CI 1.8–4.7). In England and Wales, an effect on pneumococcal meningitis was observed only after PCV13 implementation. Further studies are needed to assess pneumococcal meningitis caused by the replacing serotypes.

We compared 2 climate classification systems describing georeferenced environmental Cryptococcus gattii sensu lato isolations occurring during 1989–2016. Each system suggests the fungus was isolated in temperate climates before the 1999 outbreak on Vancouver Island, British Columbia, Canada. However, the Köppen-Geiger system is more precise and should be used to define climates where pathogens are detected.

We report 4 recent cases of nasal rhinosporidiosis in Rwanda. All patients were boys or young men living in the same district (Gatsibo District, Eastern Province), suggesting a reservoir in the area. The recent reemergence of rhinosporidiosis in Rwanda might reflect increased availability of diagnostic services rather than emerging disease.

Tools to detect human norovirus infectivity have been lacking. Using human intestinal enteroid cultures inoculated with GII.Pe-GII.4 Sydney–infected fecal samples, we determined that a real-time reverse transcription PCR cycle threshold cutoff of 30 may indicate infectious norovirus. This finding could be used to help guide infection control.

Using long-term data on incidences of Lyme disease and tickborne encephalitis, we showed that the dynamics of both diseases in central Europe are predictable from rodent host densities and climate indices. Our approach offers a simple and effective tool to predict a tickborne disease risk 1 year in advance.

We developed an electronic records methodology to programmatically estimate the date of first appearance of coccidioidomycosis symptoms in patients. We compared the diagnostic delay with overall healthcare utilization charges. Many patients (46%) had delays in diagnosis of >1 month. Billed healthcare charges before diagnosis increased with length of delay.

Tucson, Arizona, USA, is a highly coccidioidomycosis-endemic area. We conducted a retrospective review of 815 patients in Tucson over 2.7 years. Of 276 patients with coccidioidomycosis, 246 had a delay in diagnosis; median delay was 23 days. Diagnosis delay was associated with coccidioidomycosis-related costs totaling $589,053 and included extensive antibacterial drug use.

Research Letters

Diaporthe phaseolorum is a fungal plant parasite that has rarely been described as causing invasive human disease. We report a case of human soft tissue infection with Diaporthephaseolorum in a heart transplant patient with end-stage renal failure in New Zealand.

We describe emergomycosis in a patient in Uganda with HIV infection. We tested a formalin-fixed, paraffin-embedded skin biopsy to identify Emergomyces pasteurianus or a closely related pathogen by sequencing broad-range fungal PCR amplicons. Results suggest that emergomycosis is more widespread and genetically diverse than previously documented. PCR on tissue blocks may help clarify emergomycosis epidemiology.

Since its recent discovery, Bourbon virus has been isolated from a human and ticks. To assess exposure of potential vertebrate reservoirs, we assayed banked serum and plasma samples from wildlife and domestic animals in Missouri, USA, for Bourbon virus–neutralizing antibodies. We detected high seroprevalence in raccoons (50%) and white-tailed deer (86%).

Lassa fever has not been reported in Côte d’Ivoire. We performed a retrospective analysis of human serum samples collected in Côte d’Ivoire in the dry seasons (January–April) during 2015–2018. We identified a fatal human case of Lassa fever in the Bangolo District of western Côte d’Ivoire during 2015.

Since 2012, Middle East respiratory syndrome (MERS) coronavirus has infected 2,442 persons worldwide. Case-based data analysis suggests that since 2016, as many as 1,465 cases and 293–520 deaths might have been averted. Efforts to reduce the global MERS threat are working, but countries must maintain vigilance to prevent further infections.

Resistance to second-line tuberculosis drugs for patients with multidrug-resistant tuberculosis has emerged globally and is a potential risk factor for unfavorable outcomes of shorter duration drug regimens. We assessed the proportion of patients eligible for a shorter drug regimen in Uttar Pradesh, India, which had the highest rate of multidrug-resistant tuberculosis in India.

The emerging yeast Candida auris has disseminated worldwide. We report on 7 cases identified in Germany during 2015–2017. In 6 of these cases, C. auris was isolated from patients previously hospitalized abroad. Whole-genome sequencing and epidemiologic analyses revealed that all patients in Germany were infected with different strains.

Parathyridaria percutanea is an emerging fungus causing subcutaneous phaeohyphomycoses in renal transplant recipients in India. We identified P. percutanea from a patient with subcutaneous phaeohyphomycosis. From our culture collection, we identified the same fungus from 4 similar patients. We found 5 cases previously described in literature.

Cane toads, an invasive species in Australia, are resistant to fungal pathogens affecting frogs worldwide (Batrachochytrium dendrobatidis). From toad skin swabs, we detected higher proportions of bacteria with antifungal properties in Queensland, where toad and pathogen distributions overlap, than in other sites. This finding suggests that site-specific pathogen pressures help shape skin microbial communities.

We report a case of Plasmodium knowlesi malaria imported to central Europe from Southeast Asia. Laboratory suspicion of P. knowlesi infection was based on the presence of atypical developmental forms of the parasite in Giemsa-stained microscopic smears. We confirmed and documented the clinical diagnosis by molecular biology techniques.

In 2018, a previously unknown Ebola virus, Bombali virus, was discovered in Sierra Leone. We describe detection of Bombali virus in Guinea. We found viral RNA in internal organs of 3 Angolan free-tailed bats (Mops condylurus) trapped in the city of N’Zerekore and in a nearby village.

Chronic pulmonary blastomycosis is often misdiagnosed and treated as tuberculosis in disease-endemic and non–disease-endemic areas. We report the case of a 32-year-old man who after visiting Chicago, Illinois, USA, returned to India and received treatment for tuberculosis for 12 months before receiving the correct diagnosis of blastomycosis.

We present 2 fatal cases of invasive fungal disease with isavuconazole treatment failure in immunocompromised patients: one with a TR34-L98H azole–resistant Aspergillus fumigatus isolate and the other a Rhizomucor–A. fumigatus co-infection. Such patients probably require surveillance by galactomannan antigen detection and quantitative PCRs for A. fumigatus and Mucorales fungi.

Four major clades of Candida auris have been described, and all infections have clustered in these 4 clades. We identified an isolate representative of a potential fifth clade, separated from the other clades by >200,000 single-nucleotide polymorphisms, in a patient in Iran who had never traveled outside the country.

The largest outbreak of dengue fever in Tanzania is ongoing. Dengue virus type 1 was diagnosed in a traveler who returned from Tanzania to Japan. In phylogenetic analysis, the detected strain was close to the Singapore 2015 strain, providing a valuable clue for investigating the dengue outbreak in Tanzania.

Online Reports

Macaque-related injuries among primate workers can lead to a potentially fatal B virus encephalomyelitis. We describe a decision tool for evaluating the need for antiviral postexposure prophylaxis and provide a retrospective review of the injuries assessed in our center after its implementation in 2010. Among the injuries studied (n = 251), 40.6% were categorized as high-risk (prophylaxis recommended), 44.2% moderate-risk (consider prophylaxis), and 15.1% low-risk (prophylaxis not recommended). Ten percent of low-risk and 98% of high-risk injuries received prophylaxis (p<0.001). Compared with using universal postexposure prophylaxis, using a decision tool can lead to a standardization of practice and a reduction in prescriptions for antiviral medication.

Two outbreaks of epidemic polyarthritis occurred among Australian Defence Force personnel during and following short military exercises in the Shoalwater Bay Training Area, northeastern Australia, in 2016 and 2017. Ross River virus (RRV) IgM was detected in acute-phase serum samples from most patients (28/28 in 2016 and 25/31 in 2017), and RRV was recovered from 4/38 serum samples assayed (1/21 in 2016 and 3/17 in 2017). Phylogenetic analyses of RRV envelope glycoprotein E2 and nonstructural protein nsP3 nucleotide sequences segregated the RRV isolates obtained in 2016 and 2017 outbreaks into 2 distinct sublineages, suggesting that each outbreak was caused by a different strain of RRV. The spatiotemporal characteristics of the 2016 outbreak suggested that some of the infections involved human-mosquito-human transmission without any intermediate host. These outbreaks highlight the importance of personal protective measures in preventing vectorborne diseases for which no vaccine or specific prophylaxis exists.

Canine influenza virus (CIV) A(H3N2) was identified in 104 dogs in Ontario, Canada during December 28, 2017–October 30, 2018, in distinct epidemiologic clusters. High morbidity rates occurred within groups of dogs, and kennels and a veterinary clinic were identified as foci of infection. Death attributable to CIV infection occurred in 2 (2%) of 104 diagnosed cases. A combination of testing of suspected cases, contact tracing and testing, and 28-day isolation of infected dogs was used, and CIV transmission was contained in each outbreak. Dogs recently imported from Asia were implicated as the source of infection. CIV H3N2 spread rapidly within groups in this immunologically naive population; however, containment measures were apparently effective, demonstrating the potential value of prompt diagnosis and implementation of CIV control measures.

We conducted a retrospective study on all cases of pneumococcal septic arthritis (SA) in patients >18 years of age reported to the Picardie Regional Pneumococcal Network in France during 2005–2016. Among 1,062 cases of invasive pneumococcal disease, we observed 16 (1.5%) SA cases. Although SA is uncommon in adult patients, the prevalence of pneumococcal SA in the Picardie region increased from 0.69% during 2005–2010 to 2.47% during 2011–2016 after introduction of the pneumococcal 13-valent conjugate vaccine. We highlight the emergence of SA cases caused by the 23B serotype, which is not covered in the vaccine.

To investigate a cluster of Middle East respiratory syndrome (MERS) cases in a women-only dormitory in Riyadh, Saudi Arabia, in October 2015, we collected epidemiologic information, nasopharyngeal/oropharyngeal swab samples, and blood samples from 828 residents during November 2015 and December 2015–January 2016. We found confirmed infection for 19 (8 by reverse transcription PCR and 11 by serologic testing). Infection attack rates varied (2.7%–32.3%) by dormitory building. No deaths occurred. Independent risk factors for infection were direct contact with a confirmed case-patient and sharing a room with a confirmed case-patient; a protective factor was having an air conditioner in the bedroom. For 9 women from whom a second serum sample was collected, antibodies remained detectable at titers >1:20 by pseudoparticle neutralization tests (n = 8) and 90% plaque-reduction neutralization tests (n = 2). In closed high-contact settings, MERS coronavirus was highly infectious and pathogenicity was relatively low.

Edwardsiella tarda is primarily associated with gastrointestinal disease, but an increasing number of cases involving extraintestinal disease, especially E. tarda bacteremia, have been reported. Using clinical information of E. tarda bacteremia patients identified during January 2005–December 2016 in Japan, we characterized the clinical epidemiology of E. tarda bacteremia. A total of 182,668 sets of blood cultures were obtained during the study period; 40 (0.02%) sets from 26 patients were positive for E. tarda. The most common clinical manifestations were hepatobiliary infection, including cholangitis, liver abscess, and cholecystitis. Overall 30-day mortality for E. tarda bacteremia was 12%, and overall 90-day mortality was 27%. The incidence of E. tarda infection did not vary by season. We more frequently observed hepatobiliary infection in patients with E. tarda bacteremia than in patients with nonbacteremic E. tarda infections. E. tarda bacteremia is a rare entity that is not associated with high rates of death.

Research

The economic burden of West Nile virus (WNV) infection is not known for Canada. We sought to describe the direct and indirect costs of WNV infection in the province of Quebec, Canada, up to 2 years after onset of signs and symptoms. We conducted a retrospective cohort study that included WNV cases reported during 2012 and 2013. For 90 persons infected with WNV, persons with encephalitis accounted for the largest proportion of total cost; a median cost of $21,332 per patient compared with $8,124 for West Nile meningitis (p = 0.0004) and $192 for West Nile fever (p<0.0001). When results were extrapolated to all reported WNV patients, the estimated total cost for 124 symptomatic cases was ≈$1.7 million for 2012 and that for 31 symptomatic cases was ≈$430,000 for 2013. Our study provides information for the government to make informed decisions regarding public health policies and infectious diseases prevention and control programs.

The risk for invasive streptococcal infection has not been clearly quantified among persons experiencing homelessness (PEH). We compared the incidence of detected cases of invasive group A Streptococcus infection, group B Streptococcus infection, and Streptococcus pneumoniae (pneumococcal) infection among PEH with that among the general population in Anchorage, Alaska, USA, during 2002–2015. We used data from the Centers for Disease Control and Prevention’s Arctic Investigations Program surveillance system, the US Census, and the Anchorage Point-in-Time count (a yearly census of PEH). We detected a disproportionately high incidence of invasive streptococcal disease in Anchorage among PEH. Compared with the general population, PEH were 53.3 times as likely to have invasive group A Streptococcus infection, 6.9 times as likely to have invasive group B Streptococcus infection, and 36.3 times as likely to have invasive pneumococcal infection. Infection control in shelters, pneumococcal vaccination, and infection monitoring could help protect the health of this vulnerable group.

We retrospectively assessed the utility of a flow cytometry–based test quantifying the percentage of CD3+ T cells with the CD4–/CD8– phenotype for predicting tularemia diagnoses in 64 probable and confirmed tularemia patients treated during 2003–2015 and 342 controls with tularemia-like illnesses treated during 2012–2015 in the Czech Republic. The median percentage of CD3+/CD4–/CD8– T cells in peripheral blood was higher in tularemia patients (19%, 95% CI 17%–22%) than in controls (3%, 95% CI 2%–3%). When we used 8% as the cutoff, this test’s sensitivity was 0.953 and specificity 0.895 for distinguishing cases from controls. The CD3+/CD4–/CD8– T cells increased a median of 7 days before tularemia serologic test results became positive. This test supports early presumptive diagnosis of tularemia for clinically suspected cases 7–14 days before diagnosis can be confirmed by serologic testing in regions with low prevalences of tularemia-like illnesses.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a public health concern worldwide, but comprehensive analysis of risk factors for CRPA remains limited in China. We conducted a retrospective observational study of carbapenem resistance in 71,880 P. aeruginosa isolates collected in Zhejiang Province during 2015–2017. We analyzed risk factors for CRPA, including the type of clinical specimen; the year, season, and region, in which it was collected; patient information, including age, whether they were an outpatient or inpatient, and whether inpatients were in the intensive care unit or general ward; and the level of hospital submitting isolates. We found CRPA was more prevalent among isolates from patients >60 years of age and in inpatients, especially in intensive care units. In addition, specimen types and seasons in which they were collected were associated with higher rates of CRPA. Our findings can help hospitals reduce the spread of P. aeruginosa and optimize antimicrobial drug use.

Middle East respiratory syndrome coronavirus (MERS-CoV) infections in humans can cause asymptomatic to fatal lower respiratory lung disease. Despite posing a probable risk for virus transmission, asymptomatic to mild infections can go unnoticed; a lack of seroconversion among some PCR-confirmed cases has been reported. We found that a MERS-CoV spike S1 protein–based ELISA, routinely used in surveillance studies, showed low sensitivity in detecting infections among PCR-confirmed patients with mild clinical symptoms and cross-reactivity of human coronavirus OC43–positive serum samples. Using in-house S1 ELISA and protein microarray, we demonstrate that most PCR-confirmed MERS-CoV case-patients with mild infections seroconverted; nonetheless, some of these samples did not have detectable levels of virus-neutralizing antibodies. The use of a sensitive and specific serologic S1-based assay can be instrumental in the accurate estimation of MERS-CoV prevalence.

Middle East respiratory syndrome coronavirus (MERS-CoV) was detected in humans in 2012. Since then, sporadic outbreaks with primary transmission through dromedary camels to humans and outbreaks in healthcare settings have shown that MERS-CoV continues to pose a threat to human health. Several serologic assays for MERS-CoV have been developed globally. We describe a collaborative study to investigate the comparability of serologic assays for MERS-CoV and assess any benefit associated with the introduction of a standard reference reagent for MERS-CoV serology. Our study findings indicate that, when possible, laboratories should use a testing algorithm including >2 tests to ensure correct diagnosis of MERS-CoV. We also demonstrate that the use of a reference reagent greatly improves the agreement between assays, enabling more consistent and therefore more meaningful comparisons between results.

Pregnant women constitute a promising sentinel group for continuous monitoring of malaria transmission. To identify antibody signatures of recent Plasmodium falciparum exposure during pregnancy, we dissected IgG responses against VAR2CSA, the parasite antigen that mediates placental sequestration. We used a multiplex peptide-based suspension array in 2,354 samples from pregnant women from Mozambique, Benin, Kenya, Gabon, Tanzania, and Spain. Two VAR2CSA peptides of limited polymorphism were immunogenic and targeted by IgG responses readily boosted during infection and with estimated half-lives of <2 years. Seroprevalence against these peptides reflected declines and rebounds of transmission in southern Mozambique during 2004–2012, reduced exposure associated with use of preventive measures during pregnancy, and local clusters of transmission that were missed by detection of P. falciparum infections. These data suggest that VAR2CSA serology can provide a useful adjunct for the fine-scale estimation of the malaria burden among pregnant women over time and space.

Sporotrichosis is a saprozoonotic fungal infection found mostly in tropical and subtropical areas. Few cases in Madagascar have been published. To document sporotrichosis epidemiology in Madagascar, we conducted a cross-sectional study. During March 2013–June 2017, we recruited from select hospitals in Madagascar patients with chronic cutaneous lesions suggestive of dermatomycosis. Sporotrichosis was diagnosed for 63 (42.5%) of 148 patients. All but 1 patient came from the central highlands, where the prevalence was 0.21 cases/100,000 inhabitants. Frequency was high (64.7%) among patients <18 years of age. Sporotrichosis was diagnosed for 73.8% of patients with arm lesions, 32.3% with leg lesions, and 15.4% with lesions at other sites. Molecular identification identified 53 Sporothrix schenckii isolates. Among the 32 patients who were followed up, response to itraconazole was complete or major for 15 and minor for 17. Overall, endemicity of sporotrichosis in Madagascar was high, concentrated in the highlands.

In 2013, a severe earthquake and typhoon affected Bohol, Philippines. To assess the postdisaster risk for emergence of Mycobacterium tuberculosis infection in children, we conducted a cross-sectional multistage cluster study to estimate the prevalence of tuberculin skin test (TST) positivity and tuberculosis (TB) in children from 200 villages in heavily affected and less affected disaster areas. Of the 5,476 children we enrolled, 355 were TST-positive (weighted prevalence 6.4%); 16 children had active TB. Fourteen (7%) villages had >20% TST-positive prevalence. Although prevalence did not differ significantly between heavily affected and less affected areas, living in a shelter with >25 persons approached significance. TST positivity was independently associated with older age, prior TB treatment, known contact with a person with TB, and living on a geographically isolated island. We found a high TST-positive prevalence, suggesting that national programs should consider the differential vulnerability of children and the role of geographically isolated communities in TB emergence.

We genetically characterized highly pathogenic avian influenza virus A(H5N6) clade 2.3.4.4b isolates found in Germany in 2017–2018 and assessed pathogenicity of representative H5N5 and H5N6 viruses in ferrets. These viruses had low pathogenicity; however, continued characterization of related isolates is warranted because of their high potential for reassortment.

We report 2 human cases of Borrelia miyamotoi disease diagnosed in Sweden, including 1 case of meningitis in an apparently immunocompetent patient. The diagnoses were confirmed by 3 different independent PCR assays and DNA sequencing from cerebrospinal fluid, supplemented by serologic analyses.

We describe a case of hantavirus pulmonary syndrome in a patient exposed to Sin Nombre virus in a coastal county in California, USA, that had no previous record of human cases. Environmental evaluation coupled with genotypic analysis of virus isolates from the case-patient and locally trapped rodents identified the likely exposure location.

Three autochthonous cases of tick-borne encephalitis (TBE) acquired in rural areas of France where Lyme borreliosis, but not TBE, is endemic highlight the emergence of TBE in new areas. For patients with neurologic involvement who have been in regions where Ixodes ticks circulate, clinicians should test for TBE virus and other tickborne viruses.

We report human infection with simian Plasmodium cynomolgi in a tourist from Denmark who had visited forest areas in peninsular Malaysia and Thailand in August and September 2018. Because P. cynomolgi may go unnoticed by standard malaria diagnostics, this malaria species may be more common in humans than was previously thought.

In response to the 2016 Zika outbreak, Aedes aegypti mosquitoes from 38 locations across Puerto Rico were screened using Centers for Disease Control and Prevention bottle bioassays for sensitivity to insecticides used for mosquito control. All populations were resistant to pyrethroids. Naled, an organophosphate, was the most effective insecticide, killing all mosquitoes tested.

Research Letters

We estimated the incubation period and serial interval for human-to-human–transmitted avian influenza A(H7N9) virus infection using case-patient clusters from epidemics in China during 2013–2017. The median incubation period was 4 days and serial interval 9 days. China’s 10-day monitoring period for close contacts of case-patients should detect most secondary infections.

Active surveillance in high-risk sites in Cambodia has identified multiple low-pathogenicity influenza A(H7) viruses, mainly in ducks. None fall within the A/Anhui/1/2013(H7N9) lineage; however, some A(H7) viruses from 2018 show temporal and phylogenetic similarity to the H7N4 virus that caused a nonfatal infection in Jiangsu Province, China, in December 2017.

An isolated Rift Valley fever (RVF) outbreak was reported in 2018 in Free State Province, South Africa. Phylogenetic analyses based on complete genome sequences of 3 RVF viruses from blood and tissue samples indicated that they were related to a virus isolated in 2016 from a man returning to China from Angola.

We evaluated rotavirus vaccination rates in the United States by using records from a nationwide health database. From data on 519,697 infants, we found 68.6% received the entire rotavirus vaccine series. We noted pockets of undervaccination in many states, particularly in the Northeast and in some western states.

Approximately 21 human cases of infection with Mycobacterium conceptionense have been reported. However, most cases were outside the United States, and optimal treatment remains uncertain. We report a case of M. conceptionense pneumonitis in a patient with HIV/AIDS in the United States. The patient was cured with azithromycin and doxycycline.

We describe a case of facial skin infection and sinusitis caused by Mycobacterium marseillense in an immunocompetent woman in China in 2018. The infection was cleared with clarithromycin, moxifloxacin, and amikacin. Antimicrobial drug treatments could not be predicted by genetic analyses; further genetic characterization would be required to do so.

Lassa virus has been identified in 3 pygmy mice, Mus baoulei, in central Benin. The glycoprotein and nucleoprotein sequences cluster with the Togo strain. These mice may be a new reservoir for Lassa virus in Ghana, Togo, and Benin.

Mycobacterium canariasense had only been isolated in humans from blood and contaminated catheters. We report a case of pulmonary disease associated with M. canariasense infection that was identified by multilocus sequence analysis; the illness was initially ascribed to M. tuberculosis. M. canariasense should be considered a cause of respiratory infection.

Enterovirus D68 (EV-D68) causes respiratory tract infections and neurologic manifestations. We compared the clinical manifestations from 2 EV-D68 outbreaks in 2014 and 2018 and a low-activity period in 2016 among hospitalized children in central Ohio, USA, and used PCR and sequencing to enable phylogenetic comparisons. During both outbreak periods, infected children had respiratory manifestations that led to an increase in hospital admissions for asthma. The 2018 EV-D68 outbreak appeared to be milder in terms of respiratory illness, as shown by lower rates of pediatric intensive care unit admission. However, the frequency of severe neurologic manifestations was higher in 2018 than in 2014. During the same period in 2016, we noted neither an increase in EV-D68 nor a significant increase in asthma-related admissions. Phylogenetic analyses showed that EV-D68 isolates from 2018 clustered differently within clade B than did isolates from 2014 and are perhaps associated with a different EV-D68 subclade.

In 2019, influenza A(H3N2) viruses carrying an I38T substitution in the polymerase acidic gene, which confers reduced susceptibility to baloxavir, were detected in Japan in an infant without baloxavir exposure and a baloxavir-treated sibling. These viruses’ whole-genome sequences were identical, indicating human-to-human transmission. Influenza virus isolates should be monitored for baloxavir susceptibility.

Research Letters

We characterized exposures and demographics of Middle East respiratory syndrome coronavirus cases reported to the Saudi Arabia Ministry of Health during July 1–October 31, 2017, and June 1–September 16, 2018. Molecular characterization of available specimens showed that lineage 5 predominated among circulating viruses during these periods continued to cluster within lineage 5 .

Unavailability of Injectable Antimicrobial Drugs to Treat Gonorrhea and Syphilis, United States, 2016

W. S. Pearson et al.

Mutation and Diversity of Diphtheria Toxin in Corynebacterium ulcerans

A patient who had initial infection with mixed strains of drug-susceptible and multidrug-resistant tuberculosis was presumed to have acquired drug resistance before confirmation that sequential strains were genotypically distinct. Transmitted infection with mixed strains is likely underappreciated; identifying these infections requires spoligotyping and whole-genome sequencing.

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Active CME Articles

We conducted a retrospective study on all cases of pneumococcal septic arthritis (SA) in patients >18 years of age reported to the Picardie Regional Pneumococcal Network in France during 2005–2016. Among 1,062 cases of invasive pneumococcal disease, we observed 16 (1.5%) SA cases. Although SA is uncommon in adult patients, the prevalence of pneumococcal SA in the Picardie region increased from 0.69% during 2005–2010 to 2.47% during 2011–2016 after introduction of the pneumococcal 13-valent conjugate vaccine. We highlight the emergence of SA cases caused by the 23B serotype, which is not covered in the vaccine.

Edwardsiella tarda is primarily associated with gastrointestinal disease, but an increasing number of cases involving extraintestinal disease, especially E. tarda bacteremia, have been reported. Using clinical information of E. tarda bacteremia patients identified during January 2005–December 2016 in Japan, we characterized the clinical epidemiology of E. tarda bacteremia. A total of 182,668 sets of blood cultures were obtained during the study period; 40 (0.02%) sets from 26 patients were positive for E. tarda. The most common clinical manifestations were hepatobiliary infection, including cholangitis, liver abscess, and cholecystitis. Overall 30-day mortality for E. tarda bacteremia was 12%, and overall 90-day mortality was 27%. The incidence of E. tarda infection did not vary by season. We more frequently observed hepatobiliary infection in patients with E. tarda bacteremia than in patients with nonbacteremic E. tarda infections. E. tarda bacteremia is a rare entity that is not associated with high rates of death.

The risk for invasive streptococcal infection has not been clearly quantified among persons experiencing homelessness (PEH). We compared the incidence of detected cases of invasive group A Streptococcus infection, group B Streptococcus infection, and Streptococcus pneumoniae (pneumococcal) infection among PEH with that among the general population in Anchorage, Alaska, USA, during 2002–2015. We used data from the Centers for Disease Control and Prevention’s Arctic Investigations Program surveillance system, the US Census, and the Anchorage Point-in-Time count (a yearly census of PEH). We detected a disproportionately high incidence of invasive streptococcal disease in Anchorage among PEH. Compared with the general population, PEH were 53.3 times as likely to have invasive group A Streptococcus infection, 6.9 times as likely to have invasive group B Streptococcus infection, and 36.3 times as likely to have invasive pneumococcal infection. Infection control in shelters, pneumococcal vaccination, and infection monitoring could help protect the health of this vulnerable group.

To assess whether risk for Clostridioides difficile infection (CDI) is higher among older adults with cancer, we conducted a retrospective cohort study with a nested case–control analysis using population-based Surveillance, Epidemiology, and End Results–Medicare linked data for 2011. Among 93,566 Medicare beneficiaries, incident CDI and odds for acquiring CDI were higher among patients with than without cancer. Specifically, risk was significantly higher for those who had liquid tumors and higher for those who had recently diagnosed solid tumors and distant metastasis. These findings were independent of prior healthcare-associated exposure. This population-based assessment can be used to identify targets for prevention of CDI.

To evaluate a classification system to support clinical decisions for treatment of contaminated deep wounds at risk for an invasive fungal infection (IFI), we studied 246 US service members (413 wounds) injured in Afghanistan (2009–2014) who had laboratory evidence of fungal infection. A total of 143 wounds with persistent necrosis and laboratory evidence were classified as IFI; 120 wounds not meeting IFI criteria were classified as high suspicion (patients had localized infection signs/symptoms and had received antifungal medication for >10 days), and 150 were classified as low suspicion (failed to meet these criteria). IFI patients received more blood than other patients and had more severe injuries than patients in the low-suspicion group. Fungi of the order Mucorales were more frequently isolated from IFI (39%) and high-suspicion (21%) wounds than from low-suspicion (9%) wounds. Wounds that did not require immediate antifungal therapy lacked necrosis and localized signs/symptoms of infection and contained fungi from orders other than Mucorales.

We report demographic, epidemiologic, and clinical findings for a prospective cohort of pregnant women during the initial phase of Zika virus introduction into Yucatan, Mexico. We monitored 115 pregnant women for signs of active or recent Zika virus infection. The estimated cumulative incidence of Zika virus infection was 0.31 and the ratio of symptomatic to asymptomatic cases was 1.7 (range 1.3–4.0 depending on age group). Exanthema was the most sensitive clinical sign but also the least specific. Conjunctival hyperemia, joint edema, and exanthema were the combination of signs that had the highest specificity but low sensitivity. We did not find evidence of vertical transmission or fetal anomalies, likely because of the low number of pregnant women tested. We also did not find evidence of congenital disease. Our findings emphasize the limited predictive value of clinical features in areas where Zika virus cocirculates with other flaviviruses.

Surveys suggest that clinicians diverge from guidelines when treating Mycobacterium avium complex (MAC) pulmonary disease (PD). To determine prescribing patterns, we conducted a cohort study of adults >66 years of age in Ontario, Canada, with MAC or Mycobacterium xenopi PD during 2001–2013. Using linked laboratory and health administrative databases, we studied the first treatment episode (>60 continuous days of >1 of a macrolide, ethambutol, rifamycin, fluoroquinolone, linezolid, inhaled amikacin, or, for M. xenopi, isoniazid). Treatment was prescribed for 24% MAC and 15% of M. xenopi PD patients. Most commonly prescribed was the recommended combination of macrolide, ethambutol, and rifamycin, for 47% of MAC and 36% of M. xenopi PD patients. Among MAC PD patients, 20% received macrolide monotherapy and 33% received regimens associated with emergent macrolide resistance. Although the most commonly prescribed regimen was guidelines-recommended, many regimens prescribed for MAC PD were associated with emergent macrolide resistance.

Candida auris is an emerging multidrug-resistant fungus that causes hospital-associated outbreaks of invasive infections with high death rates. During 2015–2016, health authorities in Colombia detected an outbreak of C. auris. We conducted an investigation to characterize the epidemiology, transmission mechanisms, and reservoirs of this organism. We investigated 4 hospitals with confirmed cases of C. auris candidemia in 3 cities in Colombia. We abstracted medical records and collected swabs from contemporaneously hospitalized patients to assess for skin colonization. We identified 40 cases; median patient age was 23 years (IQR 4 months–56 years). Twelve (30%) patients were <1 year of age, and 24 (60%) were male. The 30-day mortality was 43%. Cases clustered in time and location; axilla and groin were the most commonly colonized sites. Temporal and spatial clustering of cases and skin colonization suggest person-to-person transmission of C. auris. These cases highlight the importance of adherence to infection control recommendations.

Lassa fever (LF) is endemic to Nigeria, where the disease causes substantial rates of illness and death. In this article, we report an analysis of the epidemiologic and clinical aspects of the LF outbreak that occurred in Nigeria during January 1–May 6, 2018. A total of 1,893 cases were reported; 423 were laboratory-confirmed cases, among which 106 deaths were recorded (case-fatality rate 25.1%). Among all confirmed cases, 37 occurred in healthcare workers. The secondary attack rate among 5,001 contacts was 0.56%. Most (80.6%) confirmed cases were reported from 3 states (Edo, Ondo, and Ebonyi). Fatal outcomes were significantly associated with being elderly; no administration of ribavirin; and the presence of a cough, hemorrhaging, and unconsciousness. The findings in this study should lead to further LF research and provide guidance to those preparing to respond to future outbreaks.

Nontuberculous mycobacteria represent an uncommon but important cause of infection of the musculoskeletal system. Such infections require aggressive medical and surgical treatment, and cases are often complicated by delayed diagnosis. We retrospectively reviewed all 14 nonspinal cases of nontuberculous mycobacterial musculoskeletal infections treated over 6 years by orthopedic surgeons at a university-affiliated tertiary referral center. All patients required multiple antimicrobial agents along with aggressive surgical treatment; 13 of 14 patients ultimately achieved cure. Four patients required amputation to control the infection. Half these patients were immunosuppressed by medications or other medical illness when they sought care at the referral center. Six cases involved joint prostheses; all ultimately required hardware removal and placement of an antimicrobial spacer for eradication of infection. Our findings highlight the importance of vigilance for nontuberculous mycobacterial musculoskeletal infection, particularly in patients who are immunosuppressed or have a history of musculoskeletal surgery.

Bacillus cereus is associated with foodborne illnesses characterized by vomiting and diarrhea. Although some B. cereus strains that cause severe extraintestinal infections and nosocomial infections are recognized as serious public health threats in healthcare settings, the genetic backgrounds of B. cereus strains causing such infections remain unknown. By conducting pulsed-field gel electrophoresis and multilocus sequence typing, we found that a novel sequence type (ST), newly registered as ST1420, was the dominant ST isolated from the cases of nosocomial infections that occurred in 3 locations in Japan in 2006, 2013, and 2016. Phylogenetic analysis showed that ST1420 strains belonged to the Cereus III lineage, which is much closer to the Anthracis lineage than to other Cereus lineages. Our results suggest that ST1420 is a prevalent ST in B. cereus strains that have caused recent nosocomial infections in Japan.

Staphylococcus aureus bacteremia (SAB) is a major cause of illness and death worldwide. We analyzed temporal trends of SAB incidence and death in Denmark during 2008–2015. SAB incidence increased 48%, from 20.76 to 30.37 per 100,000 person-years, during this period (p<0.001). The largest change in incidence was observed for persons >80 years of age: a 90% increase in the SAB rate (p<0.001). After adjusting for demographic changes, annual rates increased 4.0% (95% CI 3.0–5.0) for persons <80 years of age, 8.4% (95% CI 7.0–11.0) for persons 80–89 years of age, and 13.0% (95% CI 9.0–17.5) for persons >90 years of age. The 30-day case-fatality rate remained stable at 24%; crude population death rates increased by 53% during 2008–2015 (p<0.001). Specific causes and mechanisms for this rapid increase in SAB incidence among the elderly population remain to be clarified.

Rickettsioses are endemic to Vietnam; however, only a limited number of clinical studies have been performed on these vectorborne bacteria. We conducted a prospective hospital-based study at 2 national referral hospitals in Hanoi to describe the clinical characteristics of scrub typhus and murine typhus in northern Vietnam and to assess the diagnostic applicability of quantitative real-time PCR assays to diagnose rickettsial diseases. We enrolled 302 patients with acute undifferentiated fever and clinically suspected rickettsiosis during March 2015–March 2017. We used a standardized case report form to collect clinical information and laboratory results at the time of admission and during treatment. We confirmed scrub typhus in 103 (34.1%) patients and murine typhus in 12 (3.3%) patients. These results highlight the need for increased emphasis on training for healthcare providers for earlier recognition, prevention, and treatment of rickettsial diseases in Vietnam.

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is used as a vaccine to protect against disseminated tuberculosis (TB) and as a treatment for bladder cancer. We describe characteristics of US TB patients reported to the National Tuberculosis Surveillance System (NTSS) whose disease was attributed to BCG. We identified 118 BCG cases and 91,065 TB cases reported to NTSS during 2004–2015. Most patients with BCG were US-born (86%), older (median age 75 years), and non-Hispanic white (81%). Only 17% of BCG cases had pulmonary involvement, in contrast with 84% of TB cases. Epidemiologic features of BCG cases differed from TB cases. Clinicians can use clinical history to discern probable BCG cases from TB cases, enabling optimal clinical management. Public health agencies can use this information to quickly identify probable BCG cases to avoid inappropriately reporting BCG cases to NTSS or expending resources on unnecessary public health interventions.

Extensively drug-resistant tuberculosis (XDR TB) has extremely poor treatment outcomes in adults. Limited data are available for children. We report on clinical manifestations, treatment, and outcomes for 37 children (<15 years of age) with bacteriologically confirmed XDR TB in 11 countries. These patients were managed during 1999–2013. For the 37 children, median age was 11 years, 32 (87%) had pulmonary TB, and 29 had a recorded HIV status; 7 (24%) were infected with HIV. Median treatment duration was 7.0 months for the intensive phase and 12.2 months for the continuation phase. Thirty (81%) children had favorable treatment outcomes. Four (11%) died, 1 (3%) failed treatment, and 2 (5%) did not complete treatment. We found a high proportion of favorable treatment outcomes among children, with mortality rates markedly lower than for adults. Regimens and duration of treatment varied considerably. Evaluation of new regimens in children is required.

Infection with West Nile virus (WNV) has a well-characterized acute disease process. However, long-term consequences are less understood. We searched death records for 4,142 residents of Texas, USA, infected with WNV during 2002–2012 and identified 557 (13%) deaths. We analyzed all-cause and cause-specific deaths after WNV infection by calculating standardized mortality ratios and using statewide mortality data. Acute-phase deaths (<90 days after symptom onset) occurred in 289 (7%) of case-patients; of those deaths, 289 (92%) were cases of West Nile neuroinvasive disease (WNND). Convalescent-phase deaths (>90 days after symptom onset) occurred in 268 (7%) of the remaining 3,853 case-patients; 210 (78%) of these deaths occurred in patients with WNND. Convalescent-phase WNND case-patients showed excess deaths from infectious and renal causes; case-patients <60 years of age had increased risk for all-cause death, specifically from renal, infectious, digestive, and circulatory causes. We provide population-level evidence of increased risk for death after WNV infection resulting in WNND.

Zika virus infection during pregnancy may result in birth defects and pregnancy complications. We describe the Zika virus outbreak in pregnant women in the Dominican Republic during 2016–2017. We conducted multinomial logistic regression to identify factors associated with fetal losses and preterm birth. The Ministry of Health identified 1,282 pregnant women with suspected Zika virus infection, a substantial proportion during their first trimester. Fetal loss was reported for ≈10% of the reported pregnancies, and 3 cases of fetal microcephaly were reported. Women infected during the first trimester were more likely to have early fetal loss (adjusted odds ratio 5.9, 95% CI 3.5–10.0). Experiencing fever during infection was associated with increased odds of premature birth (adjusted odds ratio 1.65, 95% CI 1.03–2.65). There was widespread morbidity during the epidemic. Our findings strengthen the evidence for a broad range of adverse pregnancy outcomes resulting from Zika virus infection.

We conducted an observational study from January 2016 through January 2017 of patients admitted to a reference pediatric hospital in Madrid, Spain, for neurologic symptoms and enterovirus infection. Among the 30 patients, the most common signs and symptoms were fever, lethargy, myoclonic jerks, and ataxia. Real-time PCR detected enterovirus in the cerebrospinal fluid of 8 patients, nasopharyngeal aspirate in 17, and anal swab samples of 5. The enterovirus was genotyped for 25 of 30 patients; enterovirus A71 was the most common serotype (21/25) and the only serotype detected in patients with brainstem encephalitis or encephalomyelitis. Treatment was intravenous immunoglobulins for 21 patients and corticosteroids for 17. Admission to the pediatric intensive care unit was required for 14 patients. All patients survived. At admission, among patients with the most severe disease, leukocytes were elevated. For children with brainstem encephalitis or encephalomyelitis, clinicians should look for enterovirus and not limit testing to cerebrospinal fluid.

Antimicrobial drug resistance is a serious health hazard driven by overuse. Administration of antimicrobial drugs to HIV-exposed, uninfected infants, a population that is growing and at high risk for infection, is poorly studied. We therefore analyzed factors associated with antibacterial drug administration to HIV-exposed, uninfected infants during their first year of life. Our study population was 2,152 HIV-exposed, uninfected infants enrolled in the Breastfeeding, Antiretrovirals and Nutrition study in Lilongwe, Malawi, during 2004–2010. All infants were breastfed through 28 weeks of age. Antibacterial drugs were prescribed frequently (to 80% of infants), and most (67%) of the 5,329 prescriptions were for respiratory indications. Most commonly prescribed were penicillins (43%) and sulfonamides (23%). Factors associated with lower hazard for antibacterial drug prescription included receipt of cotrimoxazole preventive therapy, receipt of antiretroviral drugs, and increased age. Thus, cotrimoxazole preventive therapy may lead to fewer prescriptions for antibacterial drugs for these infants.

The effectiveness of oral HIV preexposure prophylaxis (PrEP) strongly depends on maintaining adherence. We investigated the association between substance use and PrEP adherence, as well as incident sexually transmitted infections (STIs) in a high-risk cohort of 394 participants (391 men who have sex with men and 3 transgender women) who were enrolled in a PrEP demonstration project. We assessed baseline and ongoing substance use over a 48-week period for stimulants and nonstimulant substances and for each substance separately. We measured PrEP adherence by using dried blood spots to obtain levels of tenofovir diphosphate. No differences in these levels were found between substance users and nonsubstance users. Baseline stimulant use was strongly associated (odds ratio 3.4; p<0.001) with incident STIs during the study. Thus, PrEP adherence was not decreased by substance use. Because substance users had increased rates of STIs, indicating higher-risk behavior, they might be excellent candidates for PrEP.

We summarize and analyze historical and current data regarding the reemergence of St. Louis encephalitis virus (SLEV; genus Flavivirus) in the Americas. Historically, SLEV caused encephalitis outbreaks in the United States; however, it was not considered a public health concern in the rest of the Americas. After the introduction of West Nile virus in 1999, activity of SLEV decreased considerably in the United States. During 2014–2015, SLEV caused a human outbreak in Arizona and caused isolated human cases in California in 2016 and 2017. Phylogenetic analyses indicate that the emerging SLEV in the western United States is related to the epidemic strains isolated during a human encephalitis outbreak in Córdoba, Argentina, in 2005. Ecoepidemiologic studies suggest that the emergence of SLEV in Argentina was caused by the introduction of a more pathogenic strain and increasing populations of the eared dove (amplifying host).

We evaluated formalin-fixed paraffin-embedded tissue specimens from 7 patients who died with encephalitic typhus in Hamburg, Germany, during World War II. The archived specimens included only central nervous system tissues >70 years old that had been stored at room temperature. We demonstrated successful detection of Rickettsia typhi DNA by a nested qPCR specific to prsA in 2 patients. These results indicate that R. typhi infections contributed to typhus outbreaks during World War II. Immunohistochemical analyses of brain tissue specimens of R. typhi DNA–positive and –negative specimens showed perivascular B-cell accumulation. Around blood vessels, nodular cell accumulations consisted of CD4-positive and CD8-positive T cells and CD68-positive microglia and macrophages; neutrophils were found rarely. These findings are similar to those of previously reported R. prowazekii tissue specimen testing. Because R. typhi and R. prowazekii infections can be clinically and histopathologically similar, molecular analyses should be performed to distinguish the 2 pathogens.

Human pegivirus (HPgV), previously called hepatitis G virus or GB virus C, is a lymphotropic virus with undefined pathology. Because many viruses from the family Flaviviridae, to which HPgV belongs, are neurotropic, we studied whether HPgV could infect the central nervous system. We tested serum and cerebrospinal fluid samples from 96 patients with a diagnosis of encephalitis for a variety of pathogens by molecular methods and serology; we also tested for autoantibodies against neuronal antigens. We found HPgV in serum and cerebrospinal fluid from 3 patients who had encephalitis of unclear origin; that is, all the markers that had been tested were negative. Single-strand confirmation polymorphism and next-generation sequencing analysis revealed differences between the serum and cerebrospinal fluid–derived viral sequences, which is compatible with the presence of a separate HPgV compartment in the central nervous system. It is unclear whether HPgV was directly responsible for encephalitis in these patients.

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